Xanthones from Swertia mussotii and Their α-Glycosidase Inhibitory Activities

Abstract

Two new xanthones, 1,8-dihydroxy-3-methoxyxanthone 7-O-[α-L-rhamnopyranosyl(1 → 2)-β-D-glucopyranoside] (1) and 1,8- dihydroxy-3-methoxyxanthone 7-O-[α-L-rhamnopyranosyl(1 → 3)-α-L-rhamno-pyranosyl (1 → 2)-β-D-xylopyranoside] (2), together with 26 known xanthones (3–28), were isolated from the aqueous ethanol extract of the traditional Chinese herb Swertia mussotii. Their structures were elucidated via spectroscopic analyses including 2D NMR. The inhibition of α-glucosidase by the isolated xanthones was evaluated by an in vitro high-throughput screening assay. Our results indicated that 1,3,5,8-tetrahydroxyxanthone is the best inhibitor with an IC₅₀ value of 5.33 ± 0.09 µM, while the O-glycosylated xanthones were poor α-glycosidase inhibitors.

Key words

Gentianaceae - Swertia mussotii - xanthones - α-glucosidase inhibitor - diabetes mellitus

• References

• 1 Cardona ML, Fernández MI, Pedro JR, Serrano A. Xanthones from Hypericum reflexum . Phytochemistry 1990; 29: 3003-3006
• 2 Peres V, Nagem TJ. Trioxygenated naturally occurring xanthones. Phytochemistry 1997; 44: 191-214
• 3 Peres V, Nagem TJ, de Oliveira FF. Tetraoxygenated naturally occurring xanthones. Phytochemistry 2000; 44: 683-710
• 4 Hostettmann K, Wagner H. Xanthone glycosides. Phytochemistry 1977; 16: 821-829
• 5 Louh NG, Lannang AM, Mbazoa DC, Tangmouo JG, Komguem J, Castillo P, Mofo NF, Naz Q, Lontsi D, Iqbal MC, Sondengam BL. Polyanxanthone A, B and C, three xanthones from the wood trunk of Garcinia polyantha Oliv. Phytochemistry 2008; 69: 1013-1017
• 6 Pant N, Jain DC, Bhakuni RS. Phytochemicals from genus Swertia and their biological activities. Indian J Chem B 2000; 39: 565-586
• 7 Chin Y, Jung H, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (Mangosteen). Phytochemistry 2008; 69: 754-758
• 8 Fouotsa H, Lannang AM, Mbazoa CD, Rasheed S, Marasini BP, Ali Z, Devkota KP, Kengfack AE, Shaheen F, Choudhary MI, Sewald N. Xanthones inhibitors of α-glucosidase and glycation from Garcinia nobilis . Phytochem Lett 2012; 5: 236-239
• 9 Jantan I, Saputri FC. Benzophenones and xanthones from Garcinia cantleyana var. cantleyana and their inhibitory activities on human low-density lipoprotein oxidation and platelet aggregation. Phytochemistry 2012; 80: 58-63
• 10 Zhang JS, Wang XM, Gao YT, Li GP. Studies on antioxidant activities of chemical constituents of Swertia mussotii Franch. Asian J Chem 2011; 23: 1966-1968
• 11 Uvarani C, Chandraprakash K, Sankaran M, Ata A, Mohan PS. Antioxidant and structure–activity relationships of five tetraoxygenated xanthones from Swertia minor (Griscb.) Knobl. Nat Prod Res 2012; 26: 1265-1270
• 12 Neerja P, Jain DC, Bhakuni RS. Phytochemicals from genus Swertia and their biological activities. Indian J Chem B 2000; 39: 565-586
• 13 Rukachaisirikul V, Kamkaew M, Sukavisit D, Phongpaichit S, Sawangchote P, Taylor WC. Antibacterial xanthones from the leaves of Garcinia nigrolineata . J Nat Prod 2003; 66: 1531-1535
• 14 Ito C, Itoigawa M, Takakura T, Ruangrungsi N, Enjo F, Tokuda H, Nishino H, Furukawa H. Chemical constituents of Garcinia fusca: structure elucidation of eight new xanthones and their cancer chemopreventive activity. J Nat Prod 2003; 66: 200-205
• 15 Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod 2003; 66: 1124-1127
• 16 Basnet P, Kadota S, Shimizu M, Takata Y, Kobayashi M, Namba T. Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Planta Med 1995; 61: 402-405
• 17 Tian LY, Bai X, Chen XH, Fang JB, Liu SH, Chen JC. Anti-diabetic effect of methylswertianin and bellidifolin from Swertia punicea Hemsl. and its potential mechanism. Phytomedicine 2010; 17: 533-539
• 18 Chhetri DR, Parajuli P, Subba GC. Antidiabetic plants used by Sikkim and Darjeeling Himalayan tribes, India. J Ethnopharmacol 2005; 99: 199-202
• 19 Holst JJ, McGill MA. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes mellitus: focus on bile acid sequestrants. Clin Drug Invest 2012; 32: 1-14
• 20 Israili ZH. Advances in the treatment of type 2 diabetes mellitus. Am J Ther 2011; 18: 117-152
• 21 Ghosal S, Sharma PV, Chaudhuri RK. Chemical constituents of Gentianaceae. 18. Xanthones of Swertia bimaculata . Phytochemistry 1975; 14: 2671-2675
• 22 Rana VS, Rawat MSM. A new xanthone glycoside and antioxidant constituents from the rhizomes of Swertia speciosa . Chem Biodivers 2005; 2: 1310-1315
• 23 Rezanka T, Jachymova J, Dembitsky VM. Prenylated xanthone glucosides from Uralʼs lichen Umbilicaria proboscidea . Phytochemistry 2003; 62: 607-612
• 24 Ikeya Y, Sugama K, Maruno M. Xanthone C-glycoside and acylated sugar from Polygala tenuifolia . Chem Pharm Bull 1994; 42: 2305-2308
• 25 Qiao Y, Okazaki T, Ando T, Mizoue K, Kondo K, Eguchi T, Kakinuma K. Isolation and characterization of a new pyrano[4′,3′:6, 7]naphtho[1, 2-b] xanthene antibiotic FD-594. J Antibiot 1998; 51: 282-287
• 26 Meli AL, Komguem J, Ngounou FN, Tangmouo JG, Lontsi D, Ajaz A, Iqbal MC, Ranjit R, Devkota KP, Sondengam BL. Bangangxanthone A and B, two xanthones from the stem bark of Garcinia polyantha Oliv. Phytochemistry 2005; 66: 2351-2355
• 27 Wang S, Liang X. Isolation and chemical characterization of bioactive principles from Swertia franchetiana . Dalian: Dalian Institute of Chemical Physics, Chinese Academy of Sciences; 2004
• 28 Bian QY, Luo CN, Xiao PG. Four xanthone glycosides from Swertia calycina Franch. Pharm Pharmacol Commun 1998; 4: 597-598
• 29 Otsuka H. Triptexanthosides A–E: xanthone glycosides from aerial parts of Tripterospermum japonicum . Chem Pharm Bull 1999; 47: 962-965
• 30 Qing Z, Liu YW. Studies on the constituents of Swertia kauitchensis Franch. Hubei: Hubei College of Traditional Chinese Medicine; 2003
• 31 Yao S, Tang CP, Ye Y. Secoiridoids and xanthones from Tylophora secamonoides Tsiang. J Asian Nat Prod Res 2008; 10: 591-596
• 32 Takashi H, Takeo N, Yuichi H, Keiichi F, Yukiteru K. 5,6-Dimethoxysterigmatocystin, a new metabolite from Aspergillus multicolor . Tetrahedron Lett 1997; 32: 2765-2766
• 33 Silveira ER, Falcão MJC, Menezes jr. A, Kingston DGI, Glass TE. Pentaoxygenated xanthones from Bredemeyera floribunda . Phytochemistry 1995; 39: 1433-1436
• 34 Bennett GJ, Lee HH, Lee LP. Synthesis of minor xanthones from Garcinia mangostana . J Nat Prod 1990; 53: 1463-1470
• 35 Hidehiro A, Yasuaki H, Mikio F, Yumiko H, Motonori F, Yujiro N, Yoshijiro N, Toshiro S, Kazuo T, Yoshiteru I. The chemical constituents of fresh Gentian root. J Nat Med 2007; 61: 269-279
• 36 Wang H, Ye G, Ma CH, Tang YH, Fan MS, Li ZX, Huang CG. Identification and determination of four metabolites of mangiferin in rat urine. J Pharm Biomed Anal 2007; 45: 793-798
• 37 Li S, Shi Y, Shang XY, Cui BS, Yuan Y, Chen XG, Yang YC, Shi JG. Triterpenoids from the roots of Pterospermum heterophyllum Hance. J Asian Nat Prod Res 2009; 11: 652-657
• 38 Cortez DAG, Young MCM, Marston A, Wolfender JL, Hostettmann K. Xanthones, triterpenes and a biphenyl from Kielmeyera coriacea . Phytochemistry 1998; 47: 1367-1374
• 39 Xu KP, Li FS, Liu JF, Tan JB, Zhang LH, Zeng GY, Tan GS. Studies on chemical constituents of Swertia nervosa (G. Don) Wall. Chin Pharm 2008; 43: 1612-1614
• 40 Chhetri DR, Parajuli P, Subba GC. Antidiabetic plants used by Sikkim and Darjeeling Himalayan tribes. Indian J Ethnopharmacol 2005; 99: 199-202
• 41 Tian LY, Bai X, Chen XH, Fang JB, Liu SH, Chen JC. Anti-diabetic effect of methylswertianin and bellidifolin from Swertia punicea Hemsl. and its potential mechanism. Phytomedicine 2010; 17: 533-539
• 42 Masand VH, Mahajan DT, Patil KN, Chinchkhede KD, Jawarkar RD, Hadda TB, Alafeefy AA, Shibi IG. k-NN, quantum mechanical and field similarity based analysis of xanthone derivatives as α-glucosidase inhibitors. Med Chem Res 2012; 21: 4523-4534
• 43 Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I. Facile discrimination of aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull 2007; 55: 899-901
• 44 Choudhary MI, Shah SA, Atta-ur-Rahman Khan SN, Khan MT. Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones. Steroids 2010; 75: 956-966
• 45 Wang YF, Ma L, Li Z, Du ZY, Liu Z, Qin JK, Wang XD, Huang ZS, Gu LQ, Chen ASC. Synergetic inhibition of metal ions and genistein on α-glucosidase. FEBS Lett 2004; 576: 46-50